Patrick Becker, Fiona B. Naughton, Deborah H. Brotherton, Raul Pacheco-Gomez, Oliver Beckstein, Alexander D. Cameron

The bile acid sodium symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here, we solve the crystal structure at 2.3 Å of a transporter from Neisseria meningitidis (ASBT_NM) in complex with pantoate, a potential substrate of ASBT_NM.. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBT_NM but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.

eLife. November 2023